Analyzing fractal dimension in electroconvulsive therapy: Unraveling complexity in structural and functional neuroimaging.

BACKGROUND: Numerous studies show that electroconvulsive therapy (ECT) induces hippocampal neuroplasticity, but findings are inconsistent regarding its clinical relevance. This study aims to investigate ECT-induced plasticity of anterior and posterior hippocampi using mathematical complexity measures in neuroimaging, namely Higuchi's fractal dimension (HFD) for fMRI time series and the fractal dimension of cortical morphology (FD-CM). Furthermore, we explore the potential of these complexity measures to predict ECT treatment response. METHODS: Twenty patients with a current depressive episode (16 with major depressive disorder and 4 with bipolar disorder) underwent MRI-scans before and after an ECT-series. Twenty healthy controls matched for age and sex were also scanned twice for comparison purposes. Resting-state fMRI data were processed, and HFD was computed for anterior and posterior hippocampi. Group-by-time effects for HFD in anterior and posterior hippocampi were calculated and correlations between HFD changes and improvement in depression severity were examined. For FD-CM analyses, we preprocessed structural MRI with CAT12's surface-based methods. We explored group-by-time effects for FD-CM and the predictive value of baseline HFD and FD-CM for treatment outcome. RESULTS: Patients exhibited a significant increase in bilateral hippocampal HFD from baseline to follow-up scans. Right anterior hippocampal HFD increase was associated with reductions in depression severity. We found no group differences and group-by-time effects in FD-CM. After applying a whole-brain regression analysis, we found that baseline FD-CM in the left temporal pole predicted reduction of overall depression severity after ECT. Baseline hippocampal HFD did not predict treatment outcome. CONCLUSION: This study suggests that HFD and FD-CM are promising imaging markers to investigate ECT-induced neuroplasticity associated with treatment response.

Ginkgo biloba: A Leaf of Hope in the Fight against Alzheimer's Dementia: Clinical Trial Systematic Review.

Alzheimer's disease (AD) is a stealthy and progressive neurological disorder that is a leading cause of dementia in the global elderly population, imposing a significant burden on both the elderly and society. Currently, the condition is treated with medications that alleviate symptoms. Nonetheless, these drugs may not consistently produce the desired results and can cause serious side effects. Hence, there is a vigorous pursuit of alternative options to enhance the quality of life for patients. Ginkgo biloba (GB), an herb with historical use in traditional medicine, contains bioactive compounds such as terpenoids (Ginkgolides A, B, and C), polyphenols, organic acids, and flavonoids (quercetin, kaempferol, and isorhamnetin). These compounds are associated with anti-inflammatory, antioxidant, and neuroprotective properties, making them valuable for cognitive health. A systematic search across three databases using specific keywords-GB in AD and dementia-yielded 1702 documents, leading to the selection of 15 clinical trials for synthesis. In eleven studies, GB extract/EGb 761® was shown to improve cognitive function, neuropsychiatric symptoms, and functional abilities in both dementia types. In four studies, however, there were no significant differences between the GB-treated and placebo groups. Significant improvements were observed in scores obtained from the Mini-Mental State Examination (MMSE), Short Cognitive Performance Test (SKT), and Neuropsychiatric Inventory (NPI). While the majority of synthesized clinical trials show that Ginkgo biloba has promising potential for the treatment of these conditions, more research is needed to determine optimal dosages, effective delivery methods, and appropriate pharmaceutical formulations. Furthermore, a thorough assessment of adverse effects, exploration of long-term use implications, and investigation into potential drug interactions are critical aspects that must be carefully evaluated in future studies.

Protocol for the establishment of a serine integrase-based platform for functional validation of genetic switch controllers in eukaryotic cells.

Serine integrases (Ints) are a family of site-specific recombinases (SSRs) encoded by some bacteriophages to integrate their genetic material into the genome of a host. Their ability to rearrange DNA sequences in different ways including inversion, excision, or insertion with no help from endogenous molecular machinery, confers important biotechnological value as genetic editing tools with high host plasticity. Despite advances in their use in prokaryotic cells, only a few Ints are currently used as gene editors in eukaryotes, partly due to the functional loss and cytotoxicity presented by some candidates in more complex organisms. To help expand the number of Ints available for the assembly of more complex multifunctional circuits in eukaryotic cells, this protocol describes a platform for the assembly and functional screening of serine-integrase-based genetic switches designed to control gene expression by directional inversions of DNA sequence orientation. The system consists of two sets of plasmids, an effector module and a reporter module, both sets assembled with regulatory components (as promoter and terminator regions) appropriate for expression in mammals, including humans, and plants. The complete method involves plasmid design, DNA delivery, testing and both molecular and phenotypical assessment of results. This platform presents a suitable workflow for the identification and functional validation of new tools for the genetic regulation and reprogramming of organisms with importance in different fields, from medical applications to crop enhancement, as shown by the initial results obtained. This protocol can be completed in 4 weeks for mammalian cells or up to 8 weeks for plant cells, considering cell culture or plant growth time.

Understanding monogenic Parkinson's disease at a global scale.

Until recently, about three-quarters of all monogenic Parkinson's disease (PD) studies were performed in European/White ancestry, thereby severely limiting our insights into genotype-phenotype relationships at global scale. The first systematic approach to embrace monogenic PD worldwide, The Michael J. Fox Foundation Global Monogenic PD (MJFF GMPD) Project, contacted authors of publications reporting individuals carrying pathogenic variants in known PD-causing genes. In contrast, the Global Parkinson's Genetics Program's (GP2) Monogenic Network took a different approach by targeting PD centers not yet represented in the medical literature. Here, we describe combining both efforts in a "merger project" resulting in a global monogenic PD cohort with build-up of a sustainable infrastructure to identify the multi-ancestry spectrum of monogenic PD and enable studies of factors modifying penetrance and expression of monogenic PD. This effort demonstrates the value of future research based on team science approaches to generate comprehensive and globally relevant results.

Perchlorate-Free Energetic Oxidizers Enabled by Ionic Cocrystallization.

The search for a suitable replacement for the ubiquitous oxidizer ammonium perchlorate (AP) is a top priority to enable more sustainable solid rocket motors. The oxidizing salts ammonium nitrate (AN) and ammonium dinitramide (ADN) are regarded as potential green replacements for AP, but suffer from a plethora of handling and processing issues including poor stability and a needle-like crystal morphology which inhibits dense packing; these prevent their widespread use. In the present work, ionic cocrystallization is leveraged to produce the first cocrystals of these oxidizing salts with an energetic coformer and the first such cocrystals to maintain a positive oxygen balance. The azole-based energetic molecule 5,5'-dinitro-2H,2H'-3,3″-bi-1,2,4-triazole (DNBT) is successfully cocrystallized with AN to yield the cocrystal 2AN:DNBT. Differential scanning calorimetry data confirms that AN, which in its pure form suffers from a problematic solid-state phase transition, is stabilized in the cocrystal. Application of this cocrystallization strategy to ADN produces 2ADN:DNBT, which has the highest oxygen balance of any organic cocrystal.

Predictors of anaemia in mothers and children in Uttar Pradesh, India.

OBJECTIVE: Anaemia affects more than half of Indian women and children, but the contribution of its causes remains unquantified. We examined interrelationships between Hb and nutritional, environmental, infectious and genetic determinants of anaemia in non-pregnant mothers and children in Uttar Pradesh (UP). DESIGN: We conducted a cross-sectional survey of households in twenty-five districts of UP between October and December 2016. We collected socio-demographic data, anthropometry and venous blood in 1238 non-pregnant mothers and their children. We analysed venous blood samples for malaria, Hb, ferritin, retinol, folate, Zn, vitamin B12, C-reactive protein, α1-acid glycoprotein (AGP) and ß-thalassaemia. We used path analysis to examine pathways through which predictors of anaemia were associated with Hb concentration. SETTING: Rural and urban households in twenty-five districts of UP. PARTICIPANTS: Mothers 18-49 years and children 6-59 months in UP. RESULTS: A total of 36·4 % of mothers and 56·0 % of children were anaemic, and 26·7 % of women and 44·6 % of children had Fe deficiency anaemia. Ferritin was the strongest predictor of Hb (ß (95 % CI) = 1·03 (0·80, 1·27) g/dL in women and 0·90 (0·68, 1·12) g/dL in children). In children only, red blood cell folate and AGP were negatively associated with Hb and retinol was positively associated with Hb. CONCLUSIONS: Over 70 % of mothers and children with anaemia had Fe deficiency, needing urgent attention. However, several simultaneous predictors of Hb exist, including nutrient deficiencies and inflammation. The potential of Fe interventions to address anaemia may be constrained unless coexisting determinants are jointly addressed.

Schwann cells modulate nociception in neurofibromatosis 1.

Pain of unknown etiology is frequent in individuals with the tumor predisposition syndrome neurofibromatosis 1 (NF1), even when tumors are absent. Nerve Schwann cells (SCs) were recently shown to play roles in nociceptive processing, and we find that chemogenetic activation of SCs is sufficient to induce afferent and behavioral mechanical hypersensitivity in wild-type mice. In mouse models, animals showed afferent and behavioral hypersensitivity when SCs, but not neurons, lacked Nf1. Importantly, hypersensitivity corresponded with SC-specific upregulation of mRNA encoding glial cell line-derived neurotrophic factor (GDNF), independently of the presence of tumors. Neuropathic pain-like behaviors in the NF1 mice were inhibited by either chemogenetic silencing of SC calcium or by systemic delivery of GDNF-targeting antibodies. Together, these findings suggest that alterations in SCs directly modulate mechanical pain and suggest cell-specific treatment strategies to ameliorate pain in individuals with NF1.

Influence of the freezing level on atmospheric rivers in High Mountain Asia: WRF case studies of orographic precipitation extremes.

Atmospheric rivers (ARs) reach High Mountain Asia (HMA) about 10 days per month during the winter and spring, resulting in about 20 mm day-1 of precipitation. However, a few events may exceed 100 mm day-1, providing most of the total winter precipitation and increasing the risk of precipitation-triggered landslides and flooding, particularly when the height of the height of the 0 ∘C isotherm, or freezing level is above-average. This study shows that from 1979 to 2015, integrated water vapor transport (IVT) during ARs that reach Western HMA has increased 16% while the freezing level has increased up to 35 m. HMA ARs that have an above-average freezing level result in 10-40% less frozen precipitation compared to ARs with a below-average freezing level. To evaluate the importance of these trends in the characteristics of ARs, we investigate mesoscale processes leading to orographic precipitation using Advanced Weather Research and Forecasting (ARW-WRF) simulations at 6.7 km spatial resolution. We contrast two above- and below- average freezing level AR events with otherwise broadly similar characteristics and show that with a 50-600 m increase in freezing level, the above-average AR resulted in 10-70% less frozen precipitation than the below-average event. This study contributes to a better understanding of climate change-related impacts within HMA's hydrological cycle and the associated hazards to vulnerable communities living in the region.

Fecal Metagenomics to Identify Biomarkers of Food Intake in Healthy Adults: Findings from Randomized, Controlled, Nutrition Trials.

BACKGROUND: Undigested components of the human diet affect the composition and function of the microorganisms present in the gastrointestinal tract. Techniques like metagenomic analyses allow researchers to study functional capacity, thus revealing the potential of using metagenomic data for developing objective biomarkers of food intake. OBJECTIVES: As a continuation of our previous work using 16S and metabolomic datasets, we aimed to utilize a computationally intensive, multivariate, machine-learning approach to identify fecal KEGG (Kyoto encyclopedia of genes and genomes) Orthology (KO) categories as biomarkers that accurately classify food intake. METHODS: Data were aggregated from 5 controlled feeding studies that studied the individual impact of almonds, avocados, broccoli, walnuts, barley, and oats on the adult gastrointestinal microbiota. Deoxyribonucleic acid from preintervention and postintervention fecal samples underwent shotgun genomic sequencing. After preprocessing, sequences were aligned and functionally annotated with Double Index AlignMent Of Next-generation sequencing Data v2.0.11.149 and MEtaGenome ANalyzer v6.12.2, respectively. After the count normalization, the log of the fold change ratio for resulting KOs between pre- and postintervention of the treatment group against its corresponding control was utilized to conduct differential abundance analysis. Differentially abundant KOs were used to train machine-learning models examining potential biomarkers in both single-food and multi-food models. RESULTS: We identified differentially abundant KOs in the almond (n = 54), broccoli (n = 2474), and walnut (n = 732) groups (q < 0.20), which demonstrated classification accuracies of 80%, 87%, and 86% for the almond, broccoli, and walnut groups using a random forest model to classify food intake into each food group's respective treatment and control arms, respectively. The mixed-food random forest achieved 81% accuracy. CONCLUSIONS: Our findings reveal promise in utilizing fecal metagenomics to objectively complement self-reported measures of food intake. Future research on various foods and dietary patterns will expand these exploratory analyses for eventual use in feeding study compliance and clinical settings.

Patient Perception of Physician Attire Before and After the COVID-19 Global Pandemic Began.

Introduction: This study evaluated patient preference of physician attire both before and after the coronavirus disease 2019 (COVID-19) global pandemic began. The primary outcome was patient preference of physician attire in 2017 compared to 2022 survey cohorts. Methods: An observational cross-sectional study performed at a single-site academic institution in the United States using patient survey materials. In total, 339 patients were included in the study, 161 from 2017 and 178 from 2022. Key Points: There was a statistically significant decrease in patient preference for formal attire in the clinical settings of primary care, hospital, and overall. Male patient preference for formal attire declined in primary care, emergency room, and overall; whereas female patient preference for formal attire declined in the hospital setting. For all genders, the odds ratio was statistically significantly lower in the settings of primary care clinic, hospital, and overall clinical settings. Conclusions: Patient preference for physicians wearing formal attire has decreased significantly since the COVID-19 global pandemic began.

Protocol for a randomised, multicentre, four-arm, double-blinded, placebo-controlled trial to assess the benefits and safety of iron supplementation with malaria chemoprevention to children in Malawi: IRMA trial.

INTRODUCTION: Approximately 40% of children aged 6-59 months worldwide are anaemic. Iron-containing multiple micronutrient powders (MNPs) and iron supplements (syrup/drops) are used to combat anaemia in children in different parts of the world. However, evidence for functional benefits of iron supplementation in children is scarce, and potential risks remain poorly defined, particularly concerning diarrhoea and malaria. This trial aims to determine if: (1) the efficacy of iron supplements or MNPs (containing iron) given with malaria chemoprevention is superior to malaria chemoprevention alone, or (2) if the efficacy of malaria chemoprevention alone is superior to placebo on child cognitive development. METHODS AND ANALYSIS: IRMA is a four-arm, parallel-group, double-blinded, placebo-controlled, triple-dummy, randomised trial in Southern Malawi. The study recruits 2168 infants aged 6 months, with an intervention period of 6 months and a post-intervention period of a further 6 months. Children are randomised into four arms: (1) No intervention (placebo); (2) malaria chemoprevention only; (3) MNPs and malaria chemoprevention; and (4) iron syrup and malaria chemoprevention. The primary outcome, cognitive development (Cognitive Composite Score (CogCS)), is measured at the end of the 6 months intervention. Secondary outcomes include CogCS at a further 6 months post-intervention, motor, language and behavioural development, physical growth and prevalence of anaemia and iron deficiency. Safety outcomes include incidence of malaria and other infections, and prevalence of malaria parasitaemia during and post-intervention period. ETHICS AND DISSEMINATION: The trial is approved by the National Health Sciences Research Committee (#19/01/2213) (Malawi) and the Human Research Ethics Committee (WEHI: 19/012) (Australia). Written informed consent in the local language is obtained from each participant before conducting any study-related procedure. Results will be shared with the local community and internationally with academic and policy stakeholders. TRIAL REGISTRATION NUMBER: ACTRN12620000386932.

Antibody titers of individuals vaccinated for COVID-19: A systematic review.

An important preventive measure to mitigate the COVID-19 pandemic is vaccine implementation. In creating vaccines, evoking neutralizing antibody (NAb) production is the main objective. This review determines and compares the NAb titers produced by COVID-19 vaccine recipients based on the vaccine type and the manner of administration. This review includes published articles on studies with healthy participants with a minimum age of 18 years, without previous infections, and those who were given Emergency Use License (EUL) vaccines from WHO. Bias assessment was performed using the Cochrane Risk of Bias and the Newcastle- Ottawa Scale. In all the studies, 40.82% of the primary doses were viral vector platforms. For booster doses, 50% were mRNA platforms. Messenger RNA (mRNA) vaccines have higher titers as homologous than as heterologous vaccines. However, inactivated vaccines and viral vector vaccines have lower titers as homologous than as heterologous vaccines. Meanwhile, subunit vaccines lack data for their titers. Based on the antibody titers, homologous mRNA vaccines are more viral-protective than their heterologous counterparts. Heterologous inactivated and viral vector vaccines are more protective than homologous combinations, mainly when mRNA is the other type in those heterologous combinations. This is because mRNA vaccines elicit higher immunogenicity compared to other types.

Beverage Consumption Patterns among U.S. Adolescents and Adults from a New 24-h Beverage Recall Survey Compared to the National Health and Nutrition Examination Survey (NHANES) 2017-2018.

Beverages are major dietary components of the United States (U.S.) population. Understanding the current consumption pattern of beverages is an important element in supporting healthy diets. Our objective was to assess the validity of the 24-h beverage consumption recall data collected in 2021 through a self-administered online questionnaire (referred to as the American Beverage Association-Brandscapes Worldwide survey, ABA-BSW) by comparing it to the 24-h dietary recall data collected in the 2017-2018 National Health and Nutrition Examination Survey (NHANES). Summary statistics on the reported consumption amounts and consumption occasions (COs) of 13 beverage types (e.g., bottled water, carbonated soft drinks (CSD), tea, and others) by participants aged 13-64 years were compared between ABA-BSW (n = 20,553) and NHANES (n = 4437). The average daily consumption amount among consumers of all 13 beverage types combined was higher in ABA-BSW than in NHANES (1903 mL/day vs. 1704 mL/day). Within each beverage type, the average daily consumption amounts among consumers were generally lower in ABA-BSW except for CSD, plant-based drinks, and still juices and fruit-flavored drinks. Compared to NHANES, ABA-BSW participants reported consuming a wider variety of beverage groups, a higher number of COs per day, and lower consumption amounts within a given CO. Overall, beverage consumption patterns observed in ABA-BSW and NHANES were generally similar, supporting the design and implementation of the former survey. Further, the ABA-BSW data provide additional information on the within-day temporal beverage consumption patterns among adolescents and adults in the U.S. Differences in the observed consumption patterns between the surveys may be the result of various factors, including the survey implementation method, a consumption pattern shift between the survey time periods, beverage type availability, and impact of the COVID-19 pandemic on dietary patterns.

Associations of thalamocortical networks with reduced mindfulness in alcohol use disorder.

Background: Increased mindfulness is associated with reduced alcohol consumption in patients with alcohol use disorder (AUD) after residential treatment. However, the underlying neurobiological mechanism of mindfulness in AUD is unclear. Therefore, we investigate the structural and functional alterations of the thalamocortical system with a focus on the mediodorsal thalamic nucleus (MD-TN), the default mode and the salience network (DMN/SN) which has previously been associated with mindfulness in healthy subjects. We hypothesized lower mindfulness and reduced structural and functional connectivity (FC) of the thalamocortical system, particularly in the DMN/SN in AUD. We assumed that identified neurobiological alterations in AUD are associated with impairments of mindfulness. Methods: Forty-five abstinent patients with AUD during residential treatment and 20 healthy controls (HC) were recruited. Structural and resting-state functional MRI-scans were acquired. We analysed levels of mindfulness, thalamic volumes and network centrality degree of the MD-TN using multivariate statistics. Using seed-based whole brain analyses we investigated functional connectivity (FC) of the MD-TN. We performed exploratory correlational analyses of structural and functional DMN/SN measurements with levels of mindfulness. Results: In AUD we found significantly lower levels of mindfulness, lower bilateral thalamic and left MD-TN volumes, reduced FC between MD-TN and anterior cingulum/insula and lower network centrality degree of the left MD-TN as compared to HC. In AUD, lower mindfulness was associated with various reductions of structural and functional aspects of the MD-TN. Conclusion: Our results suggest that structural and functional alterations of a network including the MD-TN and the DMN/SN underlies disturbed mindfulness in AUD.

Postnatal imaging of conjoined twins: a customized multimodality approach.

Medical imaging plays a crucial role in the management of conjoined twins. The role of imaging is to explore the anatomy, outline the shared organs and determine whether surgery is feasible. It also serves as a roadmap for successful separation. Additionally, imaging helps with counseling parents about prognosis. This review aims to illustrate recent advances in different imaging modalities and their role in the management of the various types of conjoined twins with an emphasis on relevant tips for optimal imaging.

Phytochemical Screening and Antimicrobial Activity of Methanolic Extract of Cymbopogon schoenanthus (L.) (azkhar) Collected from Afif City, Saudi Arabia.

In Saudi Arabia, Cymbopogon schoenanthus (L.) has been traditionally used to treat a variety of diseases. This study aimed to investigate the crude methanolic extract of Cymbopogon schoenanthus (L.) phytochemical, chemical composition, and antibacterial activity. Phytochemical analysis revealed the presence of tannins, poly-tannins, steroids, alkaloids, essential oils, terpenoids, and flavonoids. The presence of functional groups such as -COOH, -OH, -C=O, and CH2 was revealed via FTIR spectroscopy. 13C and 1H NMR (nuclear magnetic resonance) were used to determine the types and number of protons (hydrogen atoms) and their electronic states. Using an agar well diffusion assay, methanolic extract of Cymbopogon schoenanthus (L.) inhibited the growth of some foodborne pathogenic bacteria in zones ranging from 8 to 25 mm in diameter. The minimum inhibitory concentration (MIC) for Staphylococcus aureus was 12.5 mg/mL, whereas it was 25 mg/mL for Bacillus cereus, Klebsiella pneumoniae, and Escherichia coli. The time-kill assay revealed a sharp decline in Staphylococcus aureus and Klebsiella pneumonia after 2 h at a concentration of 150 mg/mL, while Bacillus cereus and Escherichia coli showed a gradual decline with constant concentrations of 75 to 150 mg/mL. The minimum bactericide concentration (MBC) value for Bacillus cereus, Staphylococcus aureus, and Escherichia coli was 50 mg/mL, while it was 25 mg/mL for Klebsiella pneumoniae. In conclusion, our study revealed that Cymbopogon schoenanthus (L.) methanolic extract has a significant antibacterial effect, suggesting that it could be used to treat various foodborne pathogens.

Deciphering the underlying mechanisms of the oxidative perturbations and impaired meat quality in Wooden breast myopathy by label-free quantitative MS-based proteomics.

The study aimed to investigate biochemical mechanisms occurred in Wooden breast (WB) chicken meat, with attention to the impact on meat quality. Commercial chicken breasts were classified as Normal (N, n = 12), WB-M (moderate degree; focal hardness on cranial region, n = 12) and WB-S (severe degree; extreme and diffused hardness over the entire surface, n = 12). Samples were analyzed for physico-chemical properties, oxidative damage to lipids and proteins, and discriminating sarcoplasmic proteins by using a Q-Exactive mass spectrometer. WB meat presented impaired composition and functionality and higher levels of lipid and protein oxidation markers than N meat. The proteomic profile of WB-S presents a dynamic regulation of the relevant proteins involved in redox homeostasis, carbohydrate, protein and lipid metabolisms. Proteomics results demonstrate that the physiological and metabolic processes of muscles affected by WB myopathy are involved in combating the inflammatory process and in repairing the damaged tissue by oxidative stress.

BRAZILIAN SOCIETY OF HEPATOLOGY UPDATED RECOMMENDATIONS FOR SYSTEMIC TREATMENT OF HEPATOCELLULAR CARCINOMA.

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related mortality worldwide. The Brazilian Society of Hepatology (SBH) published in 2020 the updated recommendations for the diagnosis and treatment of HCC. Since then, new data have emerged in the literature, including new drugs approved for the systemic treatment of HCC that were not available at the time. The SBH board conducted an online single-topic meeting to discuss and review the recommendations on the systemic treatment of HCC. The invited experts were asked to conduct a systematic review of the literature on each topic related to systemic treatment and to present the summary data and recommendations during the meeting. All panelists gathered together for discussion of the topics and elaboration of the updated recommendations. The present document is the final version of the reviewed manuscript containing the recommendations of SBH and its aim is to assist healthcare professionals, policy-makers, and planners in Brazil and Latin America with systemic treatment decision-making of patients with HCC.

Prevalence of early postpartum depression and associated risk factors among selected women in southern Malawi: a nested observational study.

BACKGROUND: The birth of a child should be a time of celebration. However, for many women, childbirth represents a time of great vulnerability to becoming mentally unwell, a neglected maternal morbidity. This study aimed to determine the prevalence of early postpartum depression (PPD) and its associated risk factors among women giving birth at health facilities in southern Malawi. Identifying women vulnerable to PPD will help clinicians provide appropriately targeted interventions before discharge from the maternity ward. METHOD: We conducted a nested cross-sectional study. Women were screened for early PPD using a locally validated Edinburgh Postpartum Depression Scale (EPDS) as they were discharged from the maternity ward. The prevalence of moderate or severe (EPDS ≥ 6) and severe (EPDS ≥ 9) PPD was determined, including 95% confidence intervals (CI). Data on maternal age, education and marital status, income source, religion, gravidity, and HIV status, among others, were collected during the second trimester of pregnancy, and obstetric and infant characteristics during childbirth were examined as potential risk factors for early PPD using univariable and multivariable logistic regression analyses. RESULTS: Data contributed by 636 women were analysed. Of these women, 9.6% (95% CI; 7.4-12.1%) had moderate to severe early PPD using an EPDS cut-off of ≥ 6, and 3.3% (95% CI; 2.1-5.0%) had severe early PPD using an EPDS cut-off of ≥ 9. Multivariable analyses indicated that maternal anaemia at birth (aOR; 2.65, CI; 1.49-4.71, p-value; 0.001) was associated with increased risk for moderate and/or severe early PPD, while live birth outcome (aOR; 0.15, 95% CI; 0.04-0.54, p-value; 0.004), being single compared to divorced/widowed (aOR; 0.09, 95% CI; 0.02-0.55, p-value; 0.009), and lower education level (aOR; 0.36, 95% CI; 0.20-0.65, p-value; 0.001) were associated with decreased risk. Being HIV positive (aOR; 2.88, 95% CI; 1.08-7.67, p-value; 0.035) was associated with severe PPD only. CONCLUSION: The prevalence of early PPD was slightly lower in our selected sample compared to previous reports in Malawi and was associated with maternal anaemia at birth, non-live birth, being divorced/widowed and HIV-positive status. Therefore, health workers should screen for depressive symptoms in women who are at increased risk as they are discharged from the maternity ward for early identification and treatment.

Ferric carboxymaltose versus standard-of-care oral iron to treat second-trimester anaemia in Malawian pregnant women: a randomised controlled trial.

BACKGROUND: Anaemia affects 46% of pregnancies in Africa; oral iron is recommended by WHO but uptake and adherence are suboptimal. We tested a single dose of a modern intravenous iron formulation, ferric carboxymaltose, for anaemia treatment in Malawian pregnant women. METHODS: In this open-label, individually randomised controlled trial, we enrolled women with a singleton pregnancy of 13-26 weeks' gestation in primary care and outpatient settings across two regions in southern Malawi. Women were eligible if they had capillary haemoglobin of less than 10·0 g/dL and negative malaria rapid diagnostic test. Participants were randomised by sealed envelope 1:1. Assessors for efficacy outcomes (laboratory parameters and birthweight) were masked to intervention; participants and study nurses were not masked. Participants were given ferric carboxymaltose up to 1000 mg (given once at enrolment in an outpatient primary care setting), or standard of care (60 mg elemental iron twice daily for 90 days), along with intermittent preventive malaria treatment. The primary maternal outcome was anaemia at 36 weeks' gestation. The primary neonatal outcome was birthweight. Analyses were performed in the intention-to-treat population for mothers and liveborn neonates, according to their randomisation group. Safety outcomes included incidence of adverse events during infusion and all adverse events from randomisation to 4 weeks' post partum. The trial is registered with ANZCTR, ACTRN12618001268235. The trial has completed follow-up. FINDINGS: Between Nov 12, 2018, and March 2, 2021, 21 258 women were screened, and 862 randomly assigned to ferric carboxymaltose (n=430) or standard of care (n=432). Ferric carboxymaltose did not reduce anaemia prevalence at 36 weeks' gestation compared with standard of care (179 [52%] of 341 in the ferric carboxymaltose group vs 189 [57%] of 333 in the standard of care group; prevalence ratio [PR] 0·92, 95% CI 0·81 to 1·06; p=0·27). Anaemia prevalence was numerically lower in mothers randomly assigned to ferric carboxymaltose compared with standard of care at all timepoints, although significance was only observed at 4 weeks' post-treatment (PR 0·91 [0·85 to 0·97]). Birthweight did not differ between groups (mean difference -3·1 g [-75·0 to 68·9, p=0·93). There were no infusion-related serious adverse events or differences in adverse events by any organ class (including malaria; ≥1 adverse event: ferric carboxymaltose 183 [43%] of 430 vs standard of care 170 [39%] of 432; risk ratio 1·08 [0·92 to 1·27]; p=0·34). INTERPRETATION: In this malaria-endemic sub-Saharan African setting, treatment of anaemic pregnant women with ferric carboxymaltose was safe but did not reduce anaemia prevalence at 36 weeks' gestation or increase birthweight. FUNDING: Bill & Melinda Gates Foundation (INV-010612).